Research in the Free Radical Cancer Biology Program focuses on oxidative events in cancer, including free radicals, cell redox state and effects of anticancer drugs, radiation and other types of anticancer therapy. The overall goals of the members of this program are to identify ways of manipulating cellular redox state to improve cancer therapy and to understand the changes in oxidation associated with neoplastic disease. There are four major overlapping themes within the Program's research. Theme 1 - Understanding the role of oxidative and nitrosative events and signaling in cancer biology. Theme 2 - Augmenting cancer therapy using modulation of antioxidant enzymes, free radicals or oxidative strategies Theme 3 - The role of nitric oxide in cancer biology and cancer treatment Theme 4 - Understanding why neoplasia is more frequent and sometimes has a different biology as we age. The major accomplishments of the Free Radical Cancer Biology Program over the past funding period include the findings that (a) AdMnSOD transduction is an effective treatment for animal models of human oral cancer, (b) nitric oxide augments cell cytotoxicity of doxorubicin for a malignant breast cancer cell, but not for a cardiac cells, (c) there is a role for DNA methylation in the establishment and/or maintenance of cell-type specific gene expression, (d) there is a blunted ability in old animals to buffer potentially harmful oxidants being produced within a cell following an acute stress, and (e) that the antioxidant enzyme phospholipid glutathione peroxidase influences the growth rate of cells by altering the peroxide tone. There are numerous past and present productive collaborations both between members of the Program, and with members of other Cancer Center programs. For example, the Program Project Grant in Oxidative Events in Cancer Therapy and our participation in the Aging and Cancer P20 involve many members and are highly interactive and programmatic. The Free Radical Cancer Biology Program consists of 17 members from 9 departments and 2 colleges. Peer-reviewed, research funding for this program totals $2,230,523 with $1,624,781 coming from the NCI.